Recent studies have demonstrated that there is an endogenous analgesic system. Stimulation of certain sites in the brainstem results in powerful analgesia. Such stimulus produced analgesia (SPA) is elicited from sites rich in opiate receptor and sensitive to minute amounts of microinjected morphine. Cross-tolerance for analgesia between SPA and opiates indicates a common neural mechanism for pain suppression. There is evidence that both opiate and SPA require a descending serotoninergic pathway to spinal cord. The demonstration of such a pathway from the Nucleus Raphe Magnus (NRM) and the fact that SPA is obtained from NRM prompted the present studies. Using injection of tritiated leucine and autoradiographic anatomical techniques, we have found that NRM projects directly to regions of trigeminal system and spinal dorsal horn where pain-transmission neurons are located. Preliminary single unit studies in cat spinal cord have demonstrated an NRM-induced inhibition of cells responding to high intensity stimulation. We propose to extend these studies of the spinal mechanism of NRM-induced inhibition employing intracellular recording of dorsal horn neurons, excitability testing of primary afferent fibers and dorsal root potential measurement. In order to determine the factors that activate this endogenous analgesic system, single unit studies of NRM neurons will be carried out. BIBLIOGRAPHIC REFERENCES: Basbaum AI, Clanton CH, Fields HL: Ascending projections of nucleus gigantocellularis and nucleus raphe magnus in the cat. Amer Assoc Anat, 1976 (Abstract). Fields HL, Basbaum AI, Clanton CH, Anderson SD: Raphe magnus: possible common mediator of opiate and electrically induced analgesia. Arch Neurol 33:393, 1976 (Abstract).